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Mechanism of Analgesic Effect on Prolonged Continuous Theta Burst Stimulation

Zhejiang University logo

Zhejiang University

Status

Completed

Conditions

Chronic Pain
rTMS

Treatments

Drug: Naloxone
Drug: Ketamine Hydrochloride
Device: pcTBS of M1
Drug: Saline
Device: pcTBS of DLPFC
Device: SHAM stimulation

Study type

Interventional

Funder types

Other

Identifiers

NCT05360030
RI2022089

Details and patient eligibility

About

It has been shown that prolonged continuous theta burst stimulation (pcTBS) , a relatively new repetitive transcranial magnetic simulation (rTMS) protocol, of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) decreases pain in healthy volunteers, in various experimental models. In addition, rTMS of M1 has also been shown to have analgesic effects in various chronic pain conditions, including neuropathic pain.The mechanisms underlying rTMS-induced analgesia remain unclear. Functional neuroimaging studies have shown that rTMS of M1 and DLPFC induces changes in the activity of cortical and subcortical structures involved in pain processing and modulation. Endogenous opioids and e N-methyl-D-aspartate (NMDA) receptor are known to play a major role in these processes. The investigator hypothesized that the endogenous opioids systems (EOS) and NMDA receptor might be involved in the analgesic action of pcTBS. In the first part,the investigator compares the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, the intensity of pain induced by capsaicin were used to evaluate the analgesic effects of pcTBS. If naloxone does not reverse the analgesic effect of pcTBS,The volunteers will be invited to participant the second part of the study, which the investigator compares the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after Ketamine treatment.

Full description

This study comprised 3 parallel arms corresponding to 3 types of stimulation: active stimulation of M1, active stimulation of DLPFC-pcTBS, and sham stimulation (of M1 or DLPFC). Volunteers were randomly assigned to the 3 arms. In the first part, these volunteers participated in 2 experimental sessions 1 weeks apart, in which we compared the effects of naloxone and placebo (saline), administered according to a randomized, double-blind crossover design, on pcTBS-induced analgesia. Each experimental session started with the determination of baseline pain intensity and cortical excitability as well as plasma opioid peptide concentrations. Ten minutes before pcTBS (of M1, DLPFC, or sham), the volunteer received an intravenous bolus followed by a continuous infusion of either placebo (ie, saline) or naloxone, which was continued throughout the rTMS session (2 minutes). The participant was then allowed to rest for 60 minutes. Posttreatment pain intensity, cortical excitability and plasma opioid peptide concentrations will be determined by the same procedure used at baseline.In the second part, ketamine will be delivered the same as the first part.

Enrollment

45 patients

Sex

All

Ages

18 to 85 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

1)woman or man over 18 and under 85 years old; 2)Clinical diagnosis of physical and mental health people; 3) able to cooperate in completing questionnaire.

Exclusion criteria

1)Clinical diagnosis of psychiatric disorder including major depression; 2) History of substance abuse (alcohol, drugs); 3) Past treatment with repetitive transcranial magnetic stimulation (rTMS); 4) Contraindications to rTMS (previous severe head trauma or neurosurgical intervention, past or current epilepsy, active brain tumor, intracranial hypertension, implanted ferromagnetic devices, e.g., cardiac pacemaker, neurostimulator, or cochlear implants); 5) Any difficulty to fill out questionnaires (due to language or cognitive problems);

Trial design

Primary purpose

Diagnostic

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

45 participants in 3 patient groups

active stimulation of M1
Experimental group
Description:
pcTBS was administered to the left M1 at 80% resting motor threshold (RMT), consisting of a burst of 3 pulses given at 50 Hz repeated every 5 Hz. A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline.
Treatment:
Device: pcTBS of M1
Drug: Saline
Drug: Ketamine Hydrochloride
Drug: Naloxone
active stimulation of DLPFC
Experimental group
Description:
pcTBS was administered to the left DLPFC at 80% resting motor threshold (RMT), consisting of a burst of 3 pulses given at 50 Hz repeated every 5 Hz. A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline.
Treatment:
Device: pcTBS of DLPFC
Drug: Saline
Drug: Ketamine Hydrochloride
Drug: Naloxone
SHAM stimulation
Sham Comparator group
Description:
The Sham stimulation was delivered using the same protocol, with the coil being orientated at 90° to the scalp so that the magnetic field would be delivered away from the scal
Treatment:
Device: SHAM stimulation
Drug: Saline
Drug: Ketamine Hydrochloride
Drug: Naloxone

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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